Premium
A trypanosome oligopeptidase as a target for the trypanocidal agents pentamidine, diminazene and suramin
Author(s) -
Morty Rory E.,
Troeberg Linda,
Pike Robert N.,
Jones Roy,
Nickel Peter,
Lonsdale-Eccles John D.,
Coetzer Theresa H.T.
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00914-4
Subject(s) - suramin , trypanocidal agent , pentamidine , diminazene , pharmacology , trypanosomiasis , chemistry , virology , biology , biochemistry , trypanosoma brucei , medicine , gene , pneumonia , receptor
African trypanosomes contain a cytosolic serine oligopeptidase, called OP‐Tb, that is reversibly inhibited by the active principles of three of the five most commonly used trypanocidal drugs: pentamidine, diminazene and suramin. OP‐Tb was inhibited by pentamidine in a competitive manner, and by suramin in a partial, non‐competitive manner. The inhibition of OP‐Tb by a variety of suramin analogues correlated with the trypanocidal efficacy of these analogues ( P = 0.03; by paired Student's t ‐test). Since intracellular (therapeutic) concentrations of pentamidine and suramin are reported to reach approximately 206 K i and 15 K i respectively, we suggest that these drugs may exert part of their trypanocidal activity through the inhibition of OP‐Tb.